Most therapeutic dosage forms include mixtures of one or more active pharmaceutical ingredients (APIs) with additional components referred to as excipients. APIs are substances which exert a pharmacological effect on a living tissue or organism, whether used for prevention, treatment, or cure of a disease. APIs can occur naturally, be produced synthetically or by recombinant methods, or any combination of these approaches.
Numerous methods have been devised for delivering APIs into living organisms, each with more or less success. Traditional oral therapeutic dosage forms include both solids (tablets, capsules, pills, etc.) and liquids (solutions, suspensions, emulsions, etc.). Parenteral dosage forms include solids and liquids as well as aerosols (administered by inhalers, etc.), injectables (administered with syringes, micro-needle arrays, etc.), topicals (foams, ointments, etc.), and suppositories, among other dosage forms. Although these dosage forms might be effective in delivering low molecular weight APIs, each of these methods suffers from one or more drawbacks, including the lack of bioavailability as well as the inability to completely control either the spatial or the temporal component of the API's distribution when it comes to high molecular weight APIs. These drawbacks are especially challenging for administering biotherapeutics, i.e. pharmaceutically active peptides (e.g. growth factors), proteins (e.g. enzymes, antibodies), oligonucleotides (e.g. RNA, DNA, PNA), hormones and other natural substances or similar synthetic substances, since many of these pharmacologically active biomolecules are at least partially broken down by the digestive tract or in the blood system and are subsequently delivered in suboptimal dosing to the target site.
Therefore, there is an ongoing need for improved drug-delivery methods in life sciences, including but not limited to human and veterinary medicine. One important goal for any new drug-delivery method is to deliver the desired therapeutic agent(s) to a specific place in the body over a specific and controllable period of time, i.e. controlling the delivery of one or more substances to specific organs and tissues in the body with control of the location and release over time. Methods for accomplishing this localized and time controlled delivery are known as controlled-release drug-delivery methods. Delivering APIs to specific organs and tissues in the body offers several potential advantages, including increased patient compliance, extending activity, lowering the required dose, minimizing systemic side effects, and permitting the use of more potent therapeutics. In some cases, controlled-release drug-delivery methods can even allow the administration of therapeutic agents that would otherwise be too toxic or ineffective for use.
There are five broad types of solid dosage forms for controlled-delivery oral administration: reservoir and matrix diffusive dissolution, osmotic, ion-exchange resins, and prodrugs. For parenterals, most of the above solid dosage forms are available as well as injections (intravenous, intramuscular, etc.), transdermal systems, and implants. Numerous products have been developed for both oral and parenteral administration, including depots, pumps, micro- and nano-particles.
The incorporation of APIs into polymer matrices acting as a core reservoir is one approach for controlling their delivery. Contemporary approaches for formulating such drug-delivery systems are dependent on technological capabilities as well as the specific requirements of the application. For sustained delivery systems there are two main structural approaches: the controlled release by diffusion through a barrier such as shell, coat, or membrane, and the controlled release by the intrinsic local binding strength of the API(s) to the core or to other ingredients in the core reservoir.
Another strategy for controlled delivery of therapeutic agents, especially for delivering biotherapeutics, is their incorporation into polymeric micro- and nano-particles either by covalent or cleavable linkage or by trapping or adsorption inside porous network structures. Various particle architectures can be designed, for instance core/shell structures. Typically one or more APIs are contained either in the core, in the shell, or in both components. Their concentration can vary throughout the respective component in order to modify their release pattern. Although polymeric nano-spheres can be effective in the controlled delivery of APIs, they also suffer from several disadvantages. For example, their small size can allow them to diffuse in and out of the target tissue. The use of intravenous nano-particles may also be limited due to rapid clearance by the reticuloendothelial system or macrophages Notwithstanding, polymeric micro-spheres remain an important delivery vehicle.
In view of the above, there is a need for improving drug-delivery methods and compositions.